Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium responsible for a number of pathologies, including ocular trachoma and several sexually transmitted diseases. There are many different strains of C. trachomatis, which are separated into multiple serovars based on serological differences in the chlamydial major outer membrane protein (MOMP). C. trachomatis serovars A, B, Ba, and C are responsible for ocular trachoma which can cause conjunctivitis, conjunctival scarring and corneal scarring. C. trachomatis serovars D, Da, E, F, G, H, I, Ia, J, Ja and K are responsible for oculogenital disease which can cause cervicitis, urethritis, endometritis, pelvic inflammatory disease, tubal infertility, ectopic pregnancy, neonatal conjunctivitis and infant pneumonia. Chlamydia trachomatis serovars L1, L2 and L3 are responsible for lymphogranuloma venereum, which can cause submocosa and lymph-node invasion, with necrotizing granulomas and fibrosis. (Reviewed in Brunham et al., Nature Reviews Immunology 5:149-161, 2005; Montoya, Chlamydia, p. 694-702, In Wilson et al., Eds. Current Diagnosis & Treatment in Infectious Diseases, The McGraw-Hill Companies, Inc. 2001.) Asymptomatic genital Chlamydia infections are also common, which may lead to infertility in women that are left untreated.
Chlamydia trachomatis infects mucosal epithelial cells. Like other Chlamydia, C. trachomatis undergoes a biphasic development cycle in which it begins the cycle as a metabolically inactive infectious elementary body (EB) and transforms into a metabolically active reticulate body (RB). The bacterium exists outside the host cell as an EB, which is internalized by a host cell and surrounded by an endosomal membrane forming an inclusion body, where the EB transforms into a metabolically active RB. The RB can divide by binary fusion. Within about 40-48 hours, the RB transforms back to an EB, which is released by the host cell and can infect neighboring cells. (Id.)
Chlamydia MOMPs are part of a larger family of genetically related outer membrane proteins (the OmpA family) that are heat-modifiable, surface exposed porin proteins. OmpA proteins have a structurally similar N-terminal domain that is embedded in the bacterial outer membrane. OmpA proteins have been targeted for vaccine development because of their surface exposure, high immunogenicity, and role in the interaction between the bacteria and their host cells. Specifically, Chlamydia MOMP has been a vaccine target for many researchers (Cambridge et al., Int. J. Nanomedicine 8:1759-71 (2013); Farris et al., Infection and Immunity 79(3): 986-996 (2011); Hickey et al., Vaccine 22:4306-4315 (2004); Kalbina et al., Protein Expression and Purification 80: 194-202 (2011); O'Meara et al., PLOS One 8(4): 1-14; Skelding et al., Vaccine 24:355-366 (2006), Tifrea et al., Infection and Immunity 81(5): 1741-1750 (2013)). However, a safe and effective Chlamydia vaccine remains unavailable to reduce the risk of Chlamydia infection or its associated pathogenic effects. Additional vaccine candidates and methods for making them are therefore needed.